A randomised, non-inferiority clinical trial of single-shot intrathecal morphine versus continuous wound infiltration for postoperative pain control after open pancreatoduodenectomy

BACKGROUND: Intrathecal morphine (ITM) and continuous wound infiltration (CWI) are two alternatives to thoracic epidural analgesia in major abdominal surgery, but direct comparative studies are lacking. We evaluated whether ITM is non-inferior to CWI after open pancreatoduodenectomy. METHODS: An open-label, randomised, non-inferiority clinical trial was conducted at a tertiary hospital. Adult patients undergoing elective open pancreatoduodenectomy were randomised 1:1 to receive either a single-shot ITM (0.2 mg) or bilateral preperitoneal CWI. Both groups received standardised multimodal and intravenous patient-controlled analgesia (IV-PCA). The primary outcome was mean coughing pain score, averaged across 24, 48, and 72 h following surgery, analysed for non-inferiority using the 95% confidence interval (non-inferiority margin: 1.0). Secondary outcomes included the mean resting pain score, pain score at each time point (2, 24, 48, and 72 h), IV-PCA fentanyl consumption, EuroQol 5-Dimension 5-Level utility score, and postoperative complications. RESULTS: In the per-protocol population (n = 92), ITM was non-inferior to CWI for the primary outcome (ITM: 5.7 ± 1.7 versus CWI: 6.1 ± 1.5; mean difference -0.5, 95% c.i. -1.1 to 0.2). ITM was also non-inferior to CWI regarding the mean resting pain score. ITM provided significantly lower pain scores at 2 h following surgery, both at rest and on coughing, with a sustained reduction on coughing at 24 h and reduced fentanyl consumption. Otherwise comparable, ITM increased respiratory depression and pruritus within 24 h. CONCLUSION: ITM provides non-inferior overall and superior early analgesia to CWI after open pancreatoduodenectomy, although careful monitoring for early side effects is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier (No. NCT06761989, https://clinicaltrials.gov/study/NCT06761989) registered on 30 December 2024.